REGULATION OF VASOPRESSIN MESSENGER RNA DURING AGING

水平衡异常是老年人常见的疾病 主题包括低钠血症、脱水和减轻口渴。研究 试图找出这些问题背后的机制 异常现象。这个实验室之前的研究已经证明 血浆加压素(VP)浓度正常升高及 下丘脑VP mRNA含量和大小与延长的关系 老年雄性大鼠无脱水现象。这项提议的目标是 研究造成这些缺陷的机制，并确定 如果在老年雌性大鼠身上也观察到类似的异常。两个截然不同的 假说将被检验：1)脱水失败不能增加VP 老年雄性大鼠的mRNA继发于循环中的低水平 性腺类固醇，特别是睾丸素；和2)性激素衰竭 脱水增加老年雄性大鼠VP mRNA的发生继发于 增龄相关的糖皮质激素循环水平升高。这个 第一个假设提出了潜在的性别差异问题 增龄对VP基因表达调控的影响。《公约》的具体目标 项目包括： 1.确定老年男性费舍尔是否服用睾酮344 大鼠纠正VP释放和下丘脑VP mRNA缺陷 在慢性脱水的老年雄性大鼠中先前观察到的含量。 2.确定是否与衰老相关的睾丸素分泌减少 干扰脱水诱导的VP mRNA含量增加，但不影响 VP mRNA的大小，在VP释放不足的年龄之前 观察到的。这些研究可能会为我们深入了解 维持持续性VP的VP mRNA含量与大小的关系 慢性脱水时的分泌物。 3.确定老龄化对儿童心理健康的影响是否存在性别差异 脱水诱导的VP释放和下丘脑VP mRNA大小增加 和Fisher 344大鼠的含量。 4.确定糖皮质激素是否导致VP释放不足 慢性脱水衰老大鼠的VPmRNA含量和大小。

Abnormalities of water balance are commonly encountered in elderly human subjects including hyponatremia, dehydration, and reduced thirst. Studies are proposed to attempt to identify the mechanisms underlying these abnormalities. Prior studies from this laboratory have demonstrated that the normal increases in plasma vasopressin (VP) concentration and hypothalamic VP mRNA content and size associated with prolonged dehydration are absent in aged male rats. The goal of this proposal is to study the mechanisms responsible for these deficiencies, and to determine if similar abnormalities are observed in aged female rats. Two distinct hypotheses will be tested: 1) that failure of dehydration to increase VP mRNA in aged male rats occurs secondary to the low circulating levels of gonadal steroids, particularly testosterone; and 2) that failure of dehydration to increase VP mRNA in aged male rats occurs secondary to the aging-associated elevation in circulating levels of glucocorticoids. The first hypothesis raises the issue of potential gender differences in the effect of aging on the regulation of VP mRNA. The specific goals of the project are: 1. To determine if testosterone administration to aged male Fisher 344 rats will rectify the deficits in VP release and hypothalamic VP mRNA content previously observed in chronically dehydrated aged male rats. 2. To determine if aging-associated decreases in testosterone production interfere with dehydration induced increases in VP mRNA content, but not size of VP mRNA, prior to the age at which deficits in VP release are observed. These studies may provide insights into the importance of increases in VP mRNA content versus size for maintenance of sustained VP secretion during chronic dehydration. 3. To determine if gender differences exist in the effect of aging on dehydration induced increases in VP release and hypothalamic VP mRNA size and content in Fisher 344 rats. 4. To determine if glucocorticoids contribute to the deficit in VP release and VP mRNA content and size in chronically dehydrated aged rats.